One of the main objectives of the work carried out has been to investigate the genetic mechanism of x-ray induced lethal mutations at the albino locus of the mouse resulting in multiple enzyme deficiencies. The 3 enzymes which were found to be deficient in 4 different mutant strains were glucose-6-phosphatase, tyrosine aminotransferase, and serine dehydratase. Although these enzymes occur in different compartments of the cell, they have in common a rapid perinatal development. These and other findings (e.g. the absence of a gene dosage effect in the heterozygotes) were difficult to reconcile with the idea that the mutations were due to alterations in the structural genes for the respective enzymes. As a working hypothesis, the mutations are ascribed to an alteration of a regulatory gene which controls the appearance of these enzymes at birth. Further work is contemplated in the following directions. (1) Complementation. A new albino mutation, lethal in intraline crosses, has been found to produce viable albino offspring in interline crosses with any of the 4 previously investigated mutant strains. Enzyme levels appear to be returned to normal in some of these crosses. This will be studied in detail. (2) Enzyme induction. It is possible to induce the 3 above mentioned enzymes prematurely by injecting near term fetuses or newborn mice with either glucagon or cyclic AMP. So far it has not been possible to show any effect of these inducing agents in the albino mutants. This line of investigation is being continued. (3) Endoplasmic reticulum. The albino mutants show ultrastructural defects in the endoplasmic reticulum of liver and kidney, the principal tissues where glucose-6-phosphatase occurs, but not in other tissues where this enzyme is normally absent. This finding offers an unusual opportunity for the study of morphological and biochemical differentiation of the endoplasmic reticulum. (4) Purification of glucose-6-phosphatase. Further efforts will be made to solubilize the enzyme and to produce an active immune serum.